ABSTRACT The potency of the psychoactive component of cannabis, ?9-tetrahydrocannabinol (THC), has increased from 3.7% to 30% over the last decade; yet, the impact of THC on cardiovascular disease (CVD) risk is unclear. Studies suggest that THC may play a role in adverse cardiovascular health; however, the combined levels of THC and other compounds within cannabis, such as cannabidiol (CBD), on CVD risk are understudied. Accumulating evidence suggests that the CBD has anti-inflammatory and antioxidant properties that are beneficial to the cardiovascular system. The overarching goal of this study (N=400) is to examine the impact of blood- and urine-quantified THC/CBD among 18-to-30-year-old cannabis users by route of administration, versus nonusers, on objective measures of subclinical CVD risk. The study will examine the impact of THC/CBD on subclinical CVD risk via: 1) traditional CVD risk factors (i.e., waist circumference, blood pressure, fasting lipid profile, glucose, and CRP); 2) measures of vascular function (i.e., brachial artery flow-mediated dilation testing and pulse wave velocity measurements of arterial compliance). Specific aims are to: 1) Examine the difference in measures of subclinical CVD risk between cannabis users and nonusers; 2) Analyze the difference in measures of subclinical CVD risk by route of cannabis administration; and 3) Determine the impact of THC/CBD blood and urine levels on measures of subclinical CVD risk, within the cannabis groups. Participants will be recruited into an age-, sex-, race/ethnicity-, and income-matched group (n=100 each) from an established sampling frame in the team?s studies. Group 1 will be cannabis users who most often use via blunts (cannabis rolled into a tobacco leaf). Group 2 will be cannabis users who do not smoke tobacco cigarettes and who most often use cannabis via joint (cannabis rolled in paper with no added tobacco). This group will have no tobacco exposure. Group 3 will be cannabis users who most often use cannabis via electronic device (vape). Group 4 will be nonusers of cannabis and tobacco. Measures will be collected at baseline and a repeated, confirmatory measurement at 12-months. We hypothesize that there will be a differential effect of subclinical CVD risk by route of administration; and that higher blood- and urine-quantified THC levels will be positively related to subclinical CVD risk. Pilot studies on a cohort of 50 cannabis users with similar cannabis use and subclinical CVD risk ascertainment (PI: Vidot) confirmed feasibility and informed study aims and hypotheses. We will leverage Dr. Vidot?s (epidemiologist) cannabis expertise in collaboration with a multidisciplinary team of experts: Drs. Martinez (cardiologist), Gonzalez (substance use psychologist), Reidy (forensic toxicologist), Arheart (biostatistician), Sidney (cardiovascular consultant), Anthony (design consultant), and Alshaarawy (mechanistic consultant) to accomplish the overarching goal. Study findings will identify THC/CBD levels associated with positive/deleterious CVD risk to inform cannabinoid titration for users at increased CVD risk.